Analogue compounds having the 1,2,4-oxadiazole derivative skeleton exhibit, inter alia, an antikinetoplastid activity and an anti-inflammatory action and are known as β3 adrenergic receptor agonists, muscarinic agonists, serotonin antagonists, and non-steroidal anti-inflammatories.
1,2,4-oxadiazole derivatives have been produced by the cycloaddition of a nitrile oxide to an amidoxime; by treating an acylated amidoxime with a base such as NaH, NaOEt, or pyridine; and by acylating an amidoxime with an activated carboxylic acid derivative, for example, an ester or acid chloride, followed by cyclodehydration (see, for example, Nonpatent Documents 1, 2, and 3, infra).
A one-step method is also known for the preparation of 3-acetyl- and 3-benzoylisoxazole derivatives using ammonium cerium nitrate (CAN) (see, for example, Nonpatent Document 4, infra).
It is also known that when ammonium cerium(IV) nitrate (abbreviated below as CAN(IV)) is reacted, at 80° C. in acetophenone or under reflux in acetone, with a compound having a carbon-carbon unsaturated double or triple bond, such as an alkene or alkyne, an isoxazole derivative is obtained in high yield in a single step by a 1,3-dipolar cycloaddition that proceeds via nitration of the solvent molecule and production of the nitrile oxide, and, moreover, that the same reactions occur, with an inhibition of the production of by-products and additional improvements in the yield, using ammonium cerium(III) nitrate (abbreviated below as CAN(III)) and formic acid in place of CAN(IV) (see, for example, Nonpatent Document 5, infra).
It is also known that similar isoxazole derivatives are obtained by reaction using nontoxic iron(III) nitrate (see, for example, Nonpatent Documents 6 and 7, infra).
Nonpatent Document 1: Quardrelli, P.; Invernizzi, A. G.; Falzoni, M.; Caramella, P. Tetrahedron 1997, 53, 1787.
Nonpatent Document 2: Korbonits, D.; Horvath, K. Heterocycles 1994, 37, 2051.
Nonpatent Document 3: Mathvink, R. J.; Barrtta, A. M.; Candelore, M. R.; Cascieri, M. A.; Deng, L.; Tota, L.; Strader, C. D.; Wyvratt, M. J.; Fisher, M. H.; Weber, A. E. Bioorg. Med. Chem. Lett. 1999, 9, 1869.
Nonpatent Document 4: Itoh, K.; Takahashi, S.; Ueki, T.; Sugiyama, T.; Takahashi, T. T.; Horiuchi, C. A.; Tetrahedron Lett. 2002, 43, 7035.
Nonpatent Document 5: Itoh, K.; Horiuchi, C. A. Tetrahedron 2004, 60, 1671.
Nonpatent Document 6: Tegeler, J. T.; Diamond, C. J. J. Heterocycl. Chem. 1987, 24, 697.
Nonpatent Document 7: Diaz-Ortiz, A.; Diez-Barra, E.; Hoz, A. D. L.; Moreno, A.; Gomez-Escalonilla, M. J.; Loupy, A. Heterocycles 1996, 43, 1021.